T cell development Flashcards
What happens to naïve T cells after they exit the thymus?
- Naïve T cells (CD4⁺ or CD8⁺) recirculate via blood and lymphatics through secondary lymphoid tissue (lymph nodes, spleen).
- Contact with a specific antigen (Ag) and antigen-presenting cell (APC) leads to clonal proliferation and differentiation.
- Naïve T cells become effector T cells (cytotoxic CD8⁺ or helper CD4⁺) or memory T cells.
What do cytotoxic and helper effector T cells do?
Cytotoxic effector T cells (CD8⁺): Kill infected cells.
Helper effector T cells (CD4⁺): Secrete cytokines to coordinate immune responses.
What is the role of lymphoid tissue in T cell-mediated immunity?
- T cells recognize antigen/MHC complexes on APCs.
- Hosts an array of APCs, some specialized to trap and present antigens.
- Examples: Lymph nodes and spleen.
- Activated T cell effectors leave these areas and migrate to infection sites.
How do T cells enter and move within lymph nodes?
Enter lymph nodes from blood via high endothelial venules (HEVs).
Move into the T cell area rich in dendritic cells and macrophages (APCs).
What happens to T cells that do not recognize antigen in the lymph node?
Leave via cortical sinuses into the lymphatics and re-enter circulation, ready for another round of antigen search.
How do T cells migrate and establish contact with target cells?
T cells express chemokine receptors that bind chemokines released by other cells.
CAMs mediate:
- Naïve T cell interaction with HEVs.
- T cell interaction with APCs.
- Effector T cell interaction with target cells.
How do LFA-1 and ICAM-1 function during T cell activation?
T cells initially bind APCs through low-affinity LFA-1:ICAM-1 interactions.
TCR signaling induces a conformational change in LFA-1, increasing its affinity and prolonging cell-cell contact.
What are the steps of T cell contact with APCs?
- T cells contact APCs using CAMs.
- TCR scans APC peptide/MHC complexes.
- No recognition → T cell disengages.
- Recognition → Signal from the TCR complex.
- Increased affinity of CAM interactions.
- T cell divides, and progeny differentiate into effector cells.
What three signals are required for naïve T cell activation?
Signal 1: TCR recognizes peptide/MHC on APC (via CD3 complex).
Signal 2: Co-stimulatory molecules (B7.1/2 on APC) bind CD28 on T cells.
Signal 3: Cytokines from APC bind upregulated cytokine receptors on T cells, directing differentiation.
What is the role of CTLA-4 in T cell activation?
CTLA-4 binds B7.1/2 more avidly than CD28, delivering an inhibitory signal.
Dampens T cell responses to prevent overactivation.
Why is CTLA-4 important clinically?
CTLA-4 mutations are associated with autoimmune diseases (e.g., Type 1 diabetes).
Blocking CTLA-4 enhances anti-tumor immunity (e.g., melanoma) but risks autoimmune reactions.
Which cells are professional APCs, and what do they express?
Express MHC Class II molecules.
Examples:
Dendritic cells (specialized for naïve T cell activation).
Macrophages and B cells (present antigens for effector T cell help).
What are the two types of dendritic cells and their roles?
- Myeloid DCs (conventional):
- Potent APCs that activate naïve T cells.
- Bone marrow-derived; immature forms found in epithelia.
- Mature after encountering “danger signals” (e.g., bacterial LPS via TLR4).
- Plasmacytoid DCs:
- Important in viral infections.
- Secrete Type I interferons (IFN-α, IFN-β).
- Express TLR7 and TLR9 to sense viral antigens.
How do immature dendritic cells mature and activate T cells?
- Immature DCs in peripheral tissues encounter pathogens.
- Pathogen recognition via PAMPs activates TLRs.
- TLR signaling induces CCR7 expression and pathogen antigen processing.
- CCR7 directs DC migration to lymphoid tissue and upregulates MHC and co-stimulatory molecules (e.g., B7).
- Mature DCs present antigens to naïve T cells in lymphoid tissues.
What is the role of cytokines in T cell activation?
APC-derived cytokines dictate the differentiation of activated CD4⁺ T cells into effector subsets.
